Factors important to salivary immune responses which can effectively modify colonization and/or virulence of pathogenic microbiota include ontogenic development, subclass restriction, route of antigen administration, antigen presentation, and anamnesis. In the infant a still-maturing secretory immune system is confronted with increasingly complex infectious challenges by potentially pathogenic oral flora. Later in life the pathways available for protective secretory immune responses are more varied and include a unique system for expression of secretory immunity in microenvironments throughout the oral cavity, namely, the minor salivary gland network. This proposal will explore, in infants and young children, the development of the secretory immune system through its interaction with indigenous microbiota by: 1) comparison of the development of salivary antibody to oral streptococcal antigens in ELISA-Ab with infection by oral streptococci; 2) measurement of the progressive complexity of salivary antibody responses to epitopes from an infant's own oral flora by Western blotting; 3) identification of the ontogeny measurement of initial salivary antibody response to injection of B.pertussis antigens and anamnestic responses to injected (tetanus toxoid) and orally administered (poliovirus) vaccines, in ELISA-Ab. Also explored will be the potential for mature salivary immune expression in minor (labial) salivary gland saliva (LS) by 5) identifying IgG and IgA concentration by ELISA -Ig in LS from children, adolescents, young and older adults; 6) measuring the distinctiveness of LS IgA and IgG isotypic and subclass antibody, using a) Western blot analysis of LS, parotid and serum antibody to a battery of oral antigens, and b) isoelectric focusing/Western blot analysis of antibody spectrotypes to individual antigens; and 7) exploring the potential for stimulation gLS IgA and IgG antibody and antibody-secreting peripheral blood monocytes by topical or systemic immunization with tetanus toxoid, and 8) the possibility for enhancing LS antibody responses by combining systemic immunization with local application of antigen. These studies should a) provide new basic information about the ontogeny of salivary immunity, b)identify virulence antigens which are immunogenic during the initial colonization period and which thus could be incorporated into a dental caries vaccine, c) help to clarify the role of the minor salivary gland network in oral immunity, and d) identify the potential for specific enhancement of LS immunity by immunization.